Laboratori de Fisiologia Molecular i Canalopaties, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 88, Barcelona, Spain.
Cardiovasc Res. 2012 Jul 1;95(1):29-38. doi: 10.1093/cvr/cvs139. Epub 2012 Apr 2.
Tungstate reduces blood pressure in experimental animal models of both hypertension and metabolic syndrome, although the underlying mechanisms are not fully understood. Given that the large-conductance voltage- and Ca(2+)-dependent K(+) (BK) channel is a key element in the control of arterial tone, our aim was to evaluate whether BK channel modulation by tungstate can contribute to its antihypertensive effect.
Patch-clamp studies of heterologously expressed human BK channels (α + β(1-4) subunits) revealed that cytosolic tungstate (1 mM) induced a significant left shift (∼20 mV) in the voltage-dependent activation curve only in BK channels containing αβ(1) or αβ(4) subunits, but reduced the amplitude of K(+) currents through all BK channels tested. The β(1)-dependent activation of BK channels by tungstate was enhanced at cytosolic Ca(2+) levels reached during myocyte contraction, and prevented either by removal of cytosolic Mg(2+) or by mutations rendering the channel insensitive to Mg(2+). A lower concentration of tungstate (0.1 mM) induced voltage-dependent activation of the vascular BKαβ(1) channel without reducing current amplitude, and consistently exerted a vasodilatory action on wild-type but not on β(1)-knockout mouse arteries pre-contracted with endothelin-1.
Tungstate activates BK channels in a β subunit- and Mg(2+)-dependent manner and induces vasodilatation only in mouse arteries that express the BK β(1) subunit.
钨酸盐可降低高血压和代谢综合征实验动物模型的血压，尽管其潜在机制尚不完全清楚。鉴于大电导电压和钙依赖性钾（BK）通道是控制动脉张力的关键要素，我们的目的是评估钨酸盐对 BK 通道的调节是否有助于其降压作用。
异源表达的人 BK 通道（α+β（1-4）亚基）的膜片钳研究表明，细胞溶质钨酸盐（1 mM）仅在包含αβ（1）或αβ（4）亚基的 BK 通道中引起电压依赖性激活曲线的显著左移（约 20 mV），但降低了所有测试的 BK 通道的 K+电流幅度。钨酸盐对 BK 通道的β（1）依赖性激活在肌细胞收缩期间达到的细胞溶质 Ca2+水平下增强，并且通过去除细胞溶质 Mg2+或通过使通道对 Mg2+不敏感的突变来防止。较低浓度的钨酸盐（0.1 mM）可在不降低电流幅度的情况下诱导血管 BKαβ（1）通道的电压依赖性激活，并一致地对野生型小鼠动脉发挥血管舒张作用，但对内皮素-1预收缩的β（1）敲除小鼠动脉则无作用。
钨酸盐以β亚基和 Mg2+依赖性方式激活 BK 通道，并且仅在表达 BKβ（1）亚基的小鼠动脉中诱导血管舒张。
